Pathway to Independence – an interview with Eirini Maniou Free

Let's start at the beginning, when did you first become interested in science?

I enjoyed physics and maths in high school, but the moment I really got into science was when I attended my first university lecture in developmental biology. I still remember that it was about primordial germ cells and how they migrate to populate the gonads. I was captivated by the process of cells moving together and organising to finally build an organism. I was also very lucky to have a fantastic professor, Professor Nicolas Zagris, who spent his time translating the textbook of Scott F. Gilbert into Greek to help us to understand the theoretical background. This was the person who inspired me to become a researcher.

What did you study for your undergraduate degree?

I studied biology at the University of Patras in Greece. The programme covered a wide range of topics, from zoology to plant physiology and botany, and really provided a broad perspective on biological systems. I did my undergraduate thesis on oxidative stress in Aspergillus, but that was as far as I got in my biochemistry studies! After that, I moved to the University of Bath to do a Master's in developmental biology, and then to Dundee to work on chicken gastrulation in the lab of Kees Weijer.

What did your PhD project focus on?

It was about mesoderm migration during chick gastrulation. To this day, it remains unclear how these cells navigate after they ingress through the primitive streak. We performed migration assays on freshly isolated mesoderm, and I still remember my supervisor saying that ‘this will take a little bit of optimisation’. Two years of optimisation later, our chemotaxis assays started working and we found direct evidence of chemotaxis through a type of receptors called G protein-coupled receptors. I was fortunate to be exposed to interdisciplinary work; for example, when I joined the lab, they were building a light sheet microscope from scratch, so that gave me a lot of information on advanced microscopy and quantitative methods.

What did you do after your PhD?

I did my first postdoc at University College London, in the lab of Gabriel Galea, and this is when I moved from gastrulation to neurulation. Gabriel was starting his group at the time, focusing on the biomechanics of neural tube closure in mouse embryos. I introduced the chicken model in the lab, and this allowed us to perform parallel studies with two different organisms. I really enjoyed my time at University College London, working with Gabriel as well as Andy Copp and Nick Greene, who are world-leading experts in neural tube defects. During this time, we identified force-generating mechanisms in cranial neural tube closure (Maniou et al., 2021), described a mouse model of closed neural defects (Maniou et al., 2023) and established a novel method for quantifying mechanical forces in the closing chick neural tube (Maniou et al., 2024). The latter was in collaboration with Nicola Elvassore and led to my current Fellowship in the Department of Industrial Engineering at the University of Padua.

What inspired you to switch focus to the neural tube?

I was looking to find a lab that does a lot of live imaging and works with in vivo systems. I came across Gabriel's advert, and I went for an interview. From discussions with him, I got really interested in neural tube closure and ultimately ended up joining the lab. Gabriel was very enthusiastic and gave me the impression that we would work well together. So, switching fields partly happened through chance, but it sparked my interest and I decided to pursue the topic further.

You are now at the University of Padua, Italy. What does your current postdoctoral work focus on?

My current work focuses on morphogenesis of the neural tube, which is the embryonic precursor of the brain and spine. Formation of the neural tube involves folding and closure of a flat epithelium and requires the generation of mechanical forces. So, my project combines engineering principles and computational modelling in order to map these forces and describe how they are coordinated between tissues. This is important because failure of neural tube closure leads to congenital malformations, and we cannot fully grasp the complexity of these malformations by only looking at molecular players and genetic players.

How did you hear about Development's Pathway to Independence Programme and why did you decide to apply?

I heard about the programme on Twitter last year. At that point, I was in the first year of my fellowship, so I decided to wait. It is evident that the transition to independence is very challenging, so I felt I needed all the support I could possibly get.

What do you hope to get out of the programme?

I hope to get mentorship and feedback on my research. I have already received advice from my mentor, James Briscoe, on how to improve parts of my research proposal that were unclear and to make it stronger overall. I also very much look forward to interacting with the other fellows and with The Company of Biologists. In this way, we can exchange ideas and experiences so far, and I can start building a strong foundation for my lab.

Where are you in the process of securing an independent position and what has your experience been so far?

I am currently applying for group leader positions in the UK and Europe. It is a challenging process, especially while you are trying to publish previous work and wrap up experiments. I am trying to be flexible with respect to the city, but for me it is important to find a supportive environment and a good microscopy facility. I do believe that co-location with collaborators makes a big difference and really accelerates progress.

What excites you most about becoming an independent researcher?

I'm excited by the ability to pursue my own ideas, and my vision is to make a significant contribution to our understanding of early vertebrate development.

And conversely, what do you think will be the most challenging aspect of being a PI and how will you prepare for it?

Managing people, deadlines and budgets all at once can be daunting, and I feel that, as postdocs, we are not fully prepared for the complicated role of being a PI. My current fellowship partly prepared me for this as I had to establish the use of a new model organism, the chicken embryo, in my host lab, and independently manage my grant. At the same time, I have tried to build a small team of bioengineering students. I'm learning a lot from them, because my background is in developmental biology, but I also try to inspire them and get them excited about embryology. This teaches me how to manage people, how to keep them motivated and how to balance time demands between different projects.

Would you prefer to start your own lab in a developmental biology department or an engineering department?

Ideally, I would like both, but there are only a few places that actually specialise in the application of mechanics to embryonic development. So, I would like to have at least one of the two disciplines in place. Here in Padua, I am part of a strong engineering department. I'm exposed to so many different things, from microfluidics to atomic force microscopy, but I do miss everyday interaction with developmental biologists.

What research questions would you like to address with your own group?

For the next five years, I want to focus on the interplay between tissue mechanics and biochemical signalling. Proper formation of the neural tube requires the right tissue shape and patterning, but we do not really know how mechanical inputs are integrated with molecules that induce spatial patterns. To answer this question, we have developed novel biomaterials to quantify and perturb mechanical properties in living embryos, and my aim is to use this technology to understand the interplay between mechanics and morphogens.

In your opinion, what are some of the most exciting advances in your field?

Mechanobiology is rapidly expanding, mainly due to technological advances in the past decade or so. Now, for example, we know that as early as the morula stage in mouse embryonic development, differential contractility of blastomeres mediates cell segregation and the first cell fate decision. More recently, it was shown that hydrostatic pressure can affect the competency of neural crest cells and mechanical stress was shown to induce new signalling centres during organ development. It is a very exciting time for the field, with continuous progress, and many groups are now working towards a unified biomechanical understanding of morphogenesis.

And on the other hand, what are some of the biggest questions that you think the field will address in the future?

One of the greatest challenges is trying to link mechanical properties to the molecular machinery and the acquisition of cell identity. I find it very difficult to understand what comes first. Is it that mechanics specify cell fate by bringing cells to the right location, or, depending on its location, a cell has different mechanical properties, which in turn specify fate? In the complex environment of the embryo, this is very difficult to elucidate, and this is where (even though I'm not a big fan of them) more simplified in vitro systems are needed to complete the picture.

What is it about those in vitro systems that you're not keen on?

I feel they are quite artificial. They have the advantage of simplifying these processes, but they miss the complexity of a full organism. If I was able to answer all my questions in the embryo, I would just stay there. But I realise more and more that I need to be open and combine both sides.

You mentioned that James Briscoe is acting as your mentor on the Pathway to Independence Programme. How important do you think mentorship is in navigating an academic career?

I think it is absolutely crucial. A mentor can help in shaping an academic path, but they can also help in seeing the bigger picture when the details become overwhelming. As I am writing my first grants, I often find myself thinking too much about experiments. At this point, discussion with my mentors is very helpful to bring me back to the hypothesis. I'm grateful to all the people that have acted as my mentors to date, especially my current and previous supervisors.

Finally, what do you enjoy doing outside of the lab?

I enjoy listening to live music and discovering new bands. I like different types of music, from classical to indie rock. I am also embracing the Italian lifestyle, enjoying aperitivo and spending time with my friends.

Eirini Maniou was interviewed by Laura Hankins, Reviews Editor of Development. This piece has been edited and condensed with approval from the interviewee.